Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.     

Toxicity of Toxaphene in the Rat and Beagle Dog

Toxicity of Toxaphene in the Rat and Beagle Dog. CHU, I., VILLENEUVE,D.C, SUN, C., SECOURS, V., PROCTER, B., ARNOLD, E., CLEGG, D.,REYNOLDS, L., AND VALLI, V.E. (1986). Fundam Appl. Toxicol.7, 406-418. Residues of the insecticidal mixture, toxaphene,have been found in Great Lakes fish. The purpose of the presentstudy was to assess the subchronic toxicity of toxaphene inthe rat and beagle dog. In the rat study, groups of 10 maleand 10 female animals were fed diets containing 0, 4, 20, 100,or 500 ppm of the test compound for 13 weeks. No clinical signsof toxicity or spontaneous deaths were observed. Toxaphene treatmentup to 500 ppm had no effects on weight gain or food consumption.The liver/body weight ratio and hepatic microsomal enzyme activities(phenobarbital type) were increased in both sexes fed 500 ppmof the test compound. Toxaphene at the highest dose also causedkidney enlargement in male but not in female rats. Dose-dependenthistological changes were seen in the kidney, thyroid, and liver.Changes in the liver and thyroid were considered to be adaptativebut the injury in the proximal tubules of the kidney was focallysevere. Groups of six male and six female beagle dogs were fedtoxaphene in gelatin capsules at 0, 0.2, 2.0, and 5.0 mg/kgbody wt/day for 13 weeks. Food consumption and growth rate werenot affected. All animals survived the entire treatment period.No clinical signs of toxicity were observed. The liver/bodyweight ratio and serum alkaline phosphatase were increased indogs of both sexes fed 5.0 mg/kg. Mild to moderate dose-dependenthistological changes were observed in the liver and thyroid.Toxaphene was accumulated in a dose-dependent manner in thefat and liver of dogs and rats. Based on the biochemical, histological,and residue data, it was concluded that the no-adverse-effectlevels of the pesticide were 4.0 ppm (0.35 mg/kg) for the ratand 0.2 mg/kg for the dog.     

C1-inhibitor--biochemical properties and clinical applications

C1-inhibitor (C1-INH) is an alpha-2-neuraminoglycoprotein with a molecular weight of 105,000 daltons. It has a broad spectrum control of the many blood cascades including the complement system. Inherited deficiency of this molecule has been associated with the development of hereditary angioneurotic edema (HANE), a dominant genetic disorder. The liver and monocytes are the primary sites of C1-INH synthesis. The genetic basis of dysfunctional C1-INH is a defect at the structural locus for one C1-INH gene; both the dysfunctional C1-INH gene and the normal C1-INH gene products are present in the plasma of the affected person. The absence of C1-INH permits spontaneous activation of the first component of the complement system (C1); this, in turn, activates C4 and C2. A kinin derived from C2 may be elaborated, which then increases vascular permeability. However, recent investigations have indicated that kinin activity generated from C1-INH-depleted plasma is not derived from C2 but implicates kallikrein, an enzyme which is also controlled by C1-INH, in the formation of a kinin which is most probably bradykinin. A number of therapeutic approaches have been used to treat HANE patients, including antifribrinolytic drugs such as tranexamic acid, plasma infusion, and steroids. The anabolic steroids such as danazol and stanazolol have been used widely to treat HANE patients. We discuss in this review the potential mechanisms by which danazol promotes selective synthesis of C1-INH and several other proteins in the liver.     

有机磷解毒剂的研究2.吡啶甲醛肟碘甲烷盐(简称2-PAM)的药理作用

2-吡啶甲醛肟碘甲烷盐(2-PAM)为有效的有机磷解毒剂,本文对其药理作用作了初步的观察.证明对乌拉坦麻醉猫在接近临床用量时已能产生拟肾上腺素作用.连续应用多次后出现快速耐受现象.在应用抗肾上腺素药、利血平或切除两侧肾上腺后,2-PAM作用即减弱.C₆即使用至50毫克/公斤,亦不能阻断其作用,而5毫克/公斤的阿托品几能完全取消之.对离体及在位蟾蜍心脏也表现兴奋,此作用可部分地被C₆所阻断.2-PAM对离体豚鼠肠的兴奋作用,亦可被阿托品所取消.文内对其作用机制作了初步分析.